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• W4386624270 abstract "To the Editor: We eagerly read the recent publication by Naito et al.1 Although ependymomas are the most common spinal intramedullary tumor, previous studies outlining disease progression and functional outcomes after treatment have been limited in case numbers and also biased by the inclusion of nonintramedullary subtypes. Naito et al performed a retrospective multicenter study with more exclusive histological inclusion criteria as well as a large sample size to attain a more complete analysis on the predictors of progression-free survival and functional outcomes in spinal intramedullary ependymoma (SIE) treatment. Using a multivariate regression analysis, they found that limited tumor resection and tumor recurrence resulted in poor functional outcomes. In addition, they found that solid tumor type and nongross total surgical resection were significant poor prognostic factors for progression-free survival. As the extent of surgical resection is a primary focus of this article, we feel more thorough discussion of tumor characteristics, perioperative decision-making, and operative variables is warranted. Indeed, spinal intramedullary pathologies are variable in intraoperative appearance, and how the operation is performed can potentially affect functional outcomes and progression-free survival. Presumably, the tumors that underwent subtotal or only partial resection had characteristics that did not lend themselves to safe gross total resection. A further elucidation of these characteristics would be useful in understanding how to apply these study findings in the clinical setting. For example, a more ventral or lateral tumor location may require additional transgression of critical spinal tracts leading to higher potential morbidity. In these cases, the surgeons may have been wise to avoid potential neurological worsening postoperatively at the expense of additional potential long-term morbidity. Surgeon experience also likely contributes to the extent of resection, and this topic was not addressed in this study. In addition, there were 12 cases of cerebrospinal fluid leak noted in this study. Although cerebrospinal fluid leak is a known complication of intradural surgery, it can carry significant morbidity. It would therefore be useful to understand the method of closure used in these patients (expansile duroplasty vs primary closure with or without dural sealant). The authors of this study also briefly mention the use of neuromonitoring but do not discuss their findings regarding monitoring. What percentage of patients in the study experienced neuromonitoring changes? Of these patients, how many awoke with neurological deficit? These details are of critical importance as early neuromonitoring changes (such as in the somatosensory evoked potentials) may cause some surgeons to abandon additional surgical resection. Although these details are of course not the primary objective of this study, the addition of these details would add significantly to the translation of study findings to clinical practice. To receive a definitive diagnosis of tumor type, Naito et al performed pathological analysis for every patient. Prior genetic analyses on SIE tissue have shown that the tumor commonly demonstrates loss of the 22q locus, which harbors the Neurofibromin 2 gene.2 However, while SIE frequently demonstrates loss of the 22q locus, no tumor suppressor gene has been found to be consistently altered in pathological studies. In addition to this driver mutation, which may or may not have potential for changes in clinical course and recurrence, MYCN-amplification has been shown to present in a subset of tumors and is clinically significant in its prognostication for aggressive behavior and unfavorable outcomes, particularly in reducing progression-free survival.3 We believe that additional analysis when considering molecular markers for SIE outcomes is warranted in the future when tissue sampling and analysis are already used for histological diagnosis. Naito et al performed detailed multivariate regression models with univariate inclusion models. The analysis however was not adjusted for demographic differences between comparison cohorts. The demographic characteristics of the 3 cohorts of gross total resection, subtotal resection, and biopsy or partial resection may demonstrate baseline differences. These differences may in fact be what drove the differences observed in the extent of resection. These factors are therefore potentially confounding variables in the outcomes assessed, and subgroup analysis would most likely have shown the differences. The univariate inclusion model was also set at a low threshold (P < .05), where other studies commonly set the threshold at 0.10 or 0.20 to identify variables known to be important.4,5 Tumor size, a clinically important consideration for both functional status as well as operative considerations, was evaluated in a nonstandard fashion. Univariate analysis was conducted with size as a continuous variable, and multivariate analysis was performed with a binary threshold of 35 mm, the use of which was not deliberately explained. Further clarification on thresholding of this value would help to solidify findings that tumor size was nonsignificant in final outcomes. In this article, we discuss the findings of an important article in the treatment of SIE. Naito and colleagues did a commendable job in coordinating a multicenter study of this magnitude along with interesting results regarding treatment effects on outcomes such as function and progression-free survival. To fully understand the disease process after treatment, as well as nuances of treatment, the aforementioned considerations should be taken into account in future endeavors." @default.
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• W4386624270 date "2023-09-12" @default.
• W4386624270 modified "2023-10-18" @default.
• W4386624270 title "Letter: Predictors of Progression-Free Survival in Patients With Spinal Intramedullary Ependymoma: A Multicenter Retrospective Study by the Neurospinal Society of Japan" @default.
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• W4386624270 doi "https://doi.org/10.1227/neu.0000000000002682" @default.
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